The Generative Brain

Biacabe AG, Laplanche JL, Ryder S, Baron T 2004, Distinct molecular phenotypes in bovine prion diseases (EMBO Rep 5:110-115, PMID 14710195)

A short 2004 EMBO Reports paper from the AFSSA-Lyon animal prion laboratory (now ANSES Lyon), with co-authors in Paris and at the Veterinary Laboratories Agency in Weybridge, that reported three French cattle diagnosed with BSE whose protease-resistant prion protein looked different on western blot from typical BSE. At a time when BSE was thought to be a single stable strain, it was one of the two 2004 reports, with an Italian paper on a lower-mass amyloid form, that opened the study of what are now called atypical H-type and L-type BSE. The authors left the origin open, naming a scrapie source or a rare sporadic cattle form similar to sporadic CJD as possibilities. It concerns cattle, not human patients. Information only, not medical or veterinary advice.

Key facts

  • The three atypical animals were cows aged 8, 10 and 15 years, found through routine abattoir and rendering plant testing, with no clinical signs noted in life.
  • In these cases the unglycosylated band of protease-resistant prion protein ran 0.7 to 1.3 kDa higher than in typical BSE, the diglycosylated band was less dominant, and the P4 antibody labelled strongly, whereas 55 typical French BSE cases from 2000 to 2003 were only weakly labelled by P4.
  • Sequencing of the whole prion protein gene open reading frame in two atypical and five typical cases found no difference between them, so the authors ruled out a gene variant as the explanation in the animals tested.
  • The atypical pattern resembled a control cow experimentally infected with sheep scrapie, and the authors discussed a scrapie source, strain variation in cattle or a rare sporadic cattle disease analogous to sporadic CJD as explanations, without deciding between them.
  • The paper had clear limits: only three cases, low levels of abnormal prion protein in the brain stem, no histopathology because no fixed tissue was kept, unknown frequency, and transmission studies proposed but not done.
  • Writing from the same Lyon laboratory in 2008, the authors used this work as the basis for the H-type label (higher mass, plus an extra band near 14 kDa with the SAF84 antibody) in a review of 645 French BSE cases from 2001 to 2007 that found 7 H-type and 6 L-type cases, all in cattle over 8 years old.
  • That 2008 survey estimated about 0.41 H-type and 0.35 L-type cases per million adult cattle tested, and suggested these may be sporadic forms while saying feed or scrapie exposure could not be excluded.
  • A parallel Italian paper published online in February 2004 described two older cattle with a lower-mass, amyloid plaque forming form (BASE, later L-type) resembling the MV2 subtype of sporadic CJD; it does not cite the French paper.
  • A 2012 ANSES Lyon analysis of 12 L-type and 11 H-type French cases from 2001 to 2009 found a median age of about 12 years, against about 7 for classical BSE.
  • WOAH now describes atypical BSE as H and L-type forms that arise naturally and sporadically at a very low rate in all cattle populations and are found only in older animals; they are not WOAH listed and are excluded from official BSE risk categorisation, though positive animals must be kept out of feed and food.
  • In the 2024 EU TSE surveillance summary, 980,624 cattle were tested in the EU and Northern Ireland with 3 atypical BSE cases and no classical case.

Timeline

  1. 2003Manuscript received by EMBO Reports; accepted 2003-11.
  2. 2003Published online on 19 December 2003, in the January 2004 issue (5(1):110-115).
  3. 2004Casalone and colleagues in Turin publish the second bovine amyloidotic form (BASE) online in PNAS.
  4. 2008AFSSA Lyon publishes the France 2001 to 2007 atypical BSE survey with H-type and L-type definitions.
  5. 2012ANSES Lyon paper on age and other factors in French L-type and H-type cases.
  6. 2023WOAH adopts revised BSE standards that leave atypical BSE outside risk categorisation.
  7. 2025EFSA reports 3 atypical BSE cases among 980,624 cattle tested in 2024.
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